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National audience; INTRODUCTION. Les déséquilibres glycémiques accompagnant le diabète de type 1 (DT1) peuvent conduire, au long terme, à un léger déclin des fonctions cognitives[1]. Chez les personnes non diabétiques, l’activité physique (AP) est reconnue pour ses effets bénéfiques au niveau cérébral, notamment via l’augmentation de facteurs neurotrophiques (facteur neurotrophique dérivé du cerveau, BDNF, et IGF-1). METHODOLOGIE. Chez 95 adultes DT1, des régressions multiples ascendantes ont été réalisées pour estimer les liens entre les performances à une batterie de tests cognitifs et le niveau habituel d’AP et de sédentarité (questionnaires IPAQ et MAQ) en tenant compte des concentrations sériques de BDNF et d’IGF-1 total (prélèvement sanguin) et des facteurs classiques pouvant influencer les fonctions cognitives (démographiques : âge, sexe, IMC, niveau d’éducation ; liés au DT1 : mode d’administration de l’insuline, glycémie du moment, HbA1c, nombre d’épisodes hypoglycémiques sévères durant la vie, âge du diagnostic du DT1, durée du diabète, complications micro/macrovasculaires). RESULTATS. Le niveau d’AP prédisait positivement la flexibilité mentale (performance au TMT B-A: B– 0,05 ; SE(B) 0,03 ; P=0.05 pour le MAQ, MET-h/sem et B– 0,001 ; SE(B) 0,00 ; P=0.018 pour l’IPAQ, MET-min/sem) et ce indépendamment des niveaux de sédentarité, de BDNF et d’IGF-1.Le niveau d’AP n’influençait pas les autres domaines cognitifs évalués (i.e., la vitesse de traitement et la recherche visuo-spatiale avec le TMT-A, la résistance aux interférences avec le Stroop, la mémoire spatiale avec le SMT, la mémoire de travail avec le OPSPAN). Les autres facteurs qui influençaient la plupart des domaines cognitifs étaient l’âge, le niveau d’éducation, le nombre d’épisodes hypoglycémiques sévères, et les complications macrovasculaires. CONCLUSION. L’association entre le niveau d’AP et la flexibilité mentale chez les adultes DT1 souligne l’importance de mettre en place des programmes d’AP, en vue de préserver les fonctions exécutives au long terme.

International audience; A carbon care action has been developed for a European research project focused on the development of greener vehicles. The aim of this action is to reduce and mitigate the greenhouse gases emissions due the project activities. The classical carbon assessment has been extended to consider all the activities of an international research project. For the 3.5 years project, 209 tons of CO2eq have been estimated as GHG emissions. The most important part is related to the transport despite a significant reduction of travel during the COVID-19 pandemic.; Une action Carbon Care a été menée dans le cadre d'un projet européen portant sur le développement de véhicules plus verts. L'objectif de cette action est de réduire et de compenser les émissions de gaz à effet de serre générées par les activités du projet. L'évaluation carbone classique a été étendue de façon à prendre en compte toutes les activités d'un projet de recherche international. Pour les 3,5 années du projet, les émissions de GES ont été estimées à 209 tonnes de CO2eq. La part la plus importante étant celle des transports malgré la réduction significative des voyages liée à la pandémie de Covid.

OBJECTIVES: Ever since the first research on barriers to physical activity (PA) highlighting fear of hypoglycemia as a major barrier, many studies have attempted to understand their demographic and behavioural determinants. However, no research has been conducted on whether these perceived barriers toward PA are based on real-life-experienced adverse glycemic effects of exercise. METHODS: Sixty-two adults and 53 children/adolescents living with type 1 diabetes along with their parents completed the Barriers to Physical Activity in Type 1 Diabetes-1 (BAPAD-1) questionnaire on barriers to PA. Continuous glucose-monitoring data were collected during 1 week of everyday life for 26 adults and 33 children/adolescents. Multiple linear regressions were used to explore links between BAPAD-1 scores and glycemic excursions experienced during and after everyday-life self-reported PA sessions, controlling for behavioural (accelerometry) and demographic confounders. RESULTS: In children/adolescents, the more time spent in hypoglycemia on nights after PA sessions, the more they reported hypoglycemic risk as a barrier (ß=+0.365, p=0.034). Conversely, in adults, the higher the proportion of PA sessions accompanied by a drop in blood glucose, the less hypoglycemia was a barrier (ß=-0.046, p=0.004). In parents, BAPAD-1 scores were unrelated to children/adolescents' everyday-life exercise-induced hypo/hyperglycemia. CONCLUSIONS: In children/adolescents, fear of hypoglycemia was predominant in those exposed to nocturnal hypoglycemia associated with PA sessions. In adults, fewer barriers may mean they accept a bigger drop in their glycemia during PA. This shows the importance of finding and promoting age-specific solutions to prevent exercise-induced hypoglycemia.

International audience; Carbon assessment is beginning to be widely used in research. It is used to quantify the amount of Greenhouse gases (GHG) emissions of an activity and even tend to be part of the indicators that serve to evaluate labs. Databases and tools are available. Methods as well but they have to be adapted to each case, depending on the activities of the organization or company to be studied and the way people in charge want to build their assessment. This article aims at proposing a method for the assessment of GHG emissions of research projects. Being organized around the different activities within a research project, this method takes into account all aspects of the project. It allows a good picture and analysis of GHG emissions linked to a project.

We aimed to investigate the combined effects of aerobic exercise (EXE) and cocoa flavanol (COCOA) supplementation on performance, metabolic parameters, and inflammatory and lipid profiles in obese insulin-resistant rats. Therefore, 32 male Wistar rats (230–250 g) were fed a high-fat diet and a fructose-rich beverage for 30 days to induce insulin resistance. Next, the rats were randomized into four groups, orally administered placebo solution or COCOA supplementation (45 mg·kg−1), and either remained sedentary or were subjected to EXE on a treadmill at 60% peak velocity for 30 min, for 8 weeks. Blood samples and peripheral tissues were collected and processed to analyze metabolic and inflammatory parameters, lipid profiles, and morphological parameters. Supplementation with COCOA and EXE improved physical performance and attenuated body mass gain, adipose index, and adipocyte area. When analyzed as individual interventions, supplementation with COCOA and EXE improved glucose intolerance and the lipid profile reduced the concentrations of leptin, glucose, and insulin, and reduced homeostasis assessment index (all effects were p p p p

International audience; The automotive industry is shifting to mass production of electrified vehicles. Simulation is a key step for developing these new vehicles. System simulation tools as Simcenter Amesim includes ready-to-use multi-physics libraries in that perspective. A new library is being created based on the Energetic Macroscopic Representation formalism to speed-up the battery electric vehicles (BEV) development process. The paper presents the BEV multi-level simulation where the simulations were done using 3 different levels for the battery models. By using “plug & play” method different BEV model configurations can be built in a fast, precise and systematic way.

This paper studies the effect of the granularity of a cell model on the voltage accuracy. A multi-coupled cell model with varying parameters is compared with a simpler one (varying voltage source and equivalent series resistance). The first model implies a very long and complex characterization process. The second one is very simple. Experiments are performed at different temperatures by applying a current profile corresponding to a driving cycle of an electric vehicle. Experimental results show both models can be used for $25^{\circ}\mathrm{C}$ and $10^{\circ}\mathrm{C}$ ambient temperatures with reasonable accuracy. Nevertheless, when the temperature is cold the multi-coupled model is more accurate.

International audience; Monohydrated and dihydrated calcium oxalates have been widely studied in the literature because of their role in urolithiasis, a mammal pathology responsible for the formation of stones in the kidney. It is clear that the physicochemical environment plays a crucial role in the crystal growth and the resulting morphologies of calcium oxalates. To study these processes, reliable models for the calcium oxalates’ faces, exposed to water and potential additives, are needed. Here, we have used a total surface energy minimization approach to predict the crystal morphology of the calcium oxalate monohydrate and dihydrate phases. Surface energies were calculated at density functional theory level, taking into account surface relaxation and the effect of solvation. An excellent agreement was found between theoretically predicted morphologies and their experimental counterparts obtained by SEM, clearly demonstrating the importance of the inclusion of water in the model for the prediction of morphologies.

During exercise in hypoxia, O2 delivery to brain and muscle is compromised, and oxidative stress is elicited. Cocoa flavanols (CF) have antioxidant capacities and can increase blood flow by stimulating endothelial function. We aimed to examine the effects of 7-day CF intake on oxidative stress, nitric oxide production, and tissue oxygenation in response to exercise in normobaric hypoxia (14.3% O2). In a randomized, double-blind, cross-over study, 14 well-trained male cyclists completed four trials: exercise in normoxia or hypoxia, after 7-day CF or placebo intake. Flow-mediated dilation (FMD) was measured before intake of the last dose CF or placebo. One hundred minutes later, 20-min steady-state (SS; 45% V̇o2max) and 20-min time trial (TT) (cycling) were performed. Blood samples were taken. Prefrontal and muscular oxygenation was assessed by near-infrared spectroscopy. At baseline, FMD was increased by CF. Hypoxia increased exercise-induced elevations in lipid peroxidation and antioxidant capacity. CF suppressed exercise-induced lipid peroxidation but did not influence antioxidant capacity. At rest and during SS, prefrontal and muscular oxygenation was decreased by hypoxia. CF elevated prefrontal oxygenation but did not impact muscular oxygenation. During TT, hypoxia accelerated the exercise-induced decrease in prefrontal oxygenation, but not in muscular oxygenation. During TT, CF did not alter prefrontal and muscular oxygenation. CF did not change plasma nitrite, nitrate, and arginine:citrulline. During high-intensity exercise, CF improved neither tissue oxygenation nor performance in well-trained athletes. At rest and during moderate-intensity exercise, CF reduced exercise-induced lipid peroxidation and partially restored the hypoxia-induced decline in prefrontal oxygenation. NEW & NOTEWORTHY For the first time, we showed that CF had beneficial effects on endothelial function at rest, as well as on prefrontal oxygenation at rest and during moderate-intensity exercise, both in normoxia and hypoxia. Moreover, we showed that CF intake inhibited oxidative stress during exhaustive exercise in hypoxia.

Background Transplant recipients are at risk of pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia species. Given the limitations of conventional diagnostic techniques (i.e. microscopy and culture), a polymerase chain reaction (PCR)-based assay was developed to detect Nocardia spp. on clinical samples. While this test is increasingly being used by transplant physicians, its performance characteristics are not well documented. We evaluated the performance characteristics of this test on bronchoalveolar lavage (BAL) fluid samples from lung transplant recipients (LTRs). Methods We prospectively included all BAL samples from LTRs undergoing bronchoscopy at our institution between December 2016 and June 2017 (either surveillance or clinically-indicated bronchoscopies). Presence of microbial pathogens was assessed using techniques available locally (including microscopy and 10-day culture for Nocardia). BAL samples were also sent to the French Nocardiosis Observatory (Lyon, France) for the Nocardia PCR-based assay. Transplant physicians and patients were blinded to the Nocardia PCR results. Results We included 29 BAL samples from 21 patients (18 surveillance and 11 clinically-indicated bronchoscopies). Nocardiosis was not diagnosed in any of these patients by conventional techniques. However, Nocardia PCR was positive in five BAL samples from five of the patients (24%, 95% confidence interval: 11–45%); four were asymptomatic and undergoing surveillance bronchoscopy, and one was symptomatic and was later diagnosed with influenza virus infection. None of the five PCR-positive patients died or were diagnosed with nocardiosis during the median follow-up of 21 months after the index bronchoscopy (range: 20–23 months). Conclusions In this prospective study, Nocardia PCR was positive on BAL fluid from one fourth of the LTRs. Nocardia PCR-based assays should be used with caution on respiratory samples from LTRs because of the possible detection of airway colonization using this technique. Larger studies are required to determine the usefulness of the Nocardia PCR-based assay in transplant recipients., SCOPUS: ar.j, info:eu-repo/semantics/published

Exercise is known to have beneficial effects on cognitive function. This effect is greatly favored by an exercise-induced increase in neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), especially with high-intensity exercises (HIE). As a complication of type 1 diabetes (T1D), a cognitive decline may occur, mostly ascribed to hypoglycaemia and chronic hyperglycaemia. Therefore, the purpose of this study was to examine the effects of acute HIE on cognitive function and neurotrophins in T1D and matched controls. Ten trained T1D (8 males, 2 females) participants and their matched (by age, sex, fitness level) controls were evaluated on 2 occasions after familiarization: a maximal test to exhaustion and an HIE bout (10 intervals of 60 s at 90% of their maximal wattage followed by 60 s at 50 W). Cognitive tests and analyses of serum BDNF, IGF-1, and free insulin were performed before and after HIE and following 30 min of recovery. At baseline, cognitive performance was better in the controls compared with the T1D participants (p < 0.05). After exercise, no significant differences in cognitive performance were detected. BDNF levels were significantly higher and IGF-1 levels were significantly lower in T1D compared with the control group (p < 0.05) at all time points. Exercise increased BDNF and IGF-1 levels in a comparable percentage in both groups (p < 0.05). In conclusion, although resting levels of serum BDNF and IGF-1 were altered by T1D, comparable increasing effects on BDNF and IGF-1 in T1D and healthy participants were found. Therefore, regularly repeating acute HIE could be a promising strategy for brain health in T1D.

A capability machine is a type of CPU allowing fine-grained privilege separation using capabilities, machine words that represent certain kinds of authority. We present a mathematical model and accompanying proof methods that can be used for formal verification of functional correctness of programs running on a capability machine, even when they invoke and are invoked by unknown (and possibly malicious) code. We use a program logic called Cerise for reasoning about known code, and an associated logical relation, for reasoning about unknown code. The logical relation formally captures the capability safety guarantees provided by the capability machine. The Cerise program logic, logical relation, and all the examples considered in the paper have been mechanized using the Iris program logic framework in the Coq proof assistant. The methodology we present underlies recent work of the authors on formal reasoning about capability machines [Georges et al. 2021; Skorstengaard et al. 2019a; Van Strydonck et al. 2021], but was left somewhat implicit in those publications. In this paper we present a pedagogical introduction to the methodology, in a simpler setting (no exotic capabilities), and starting from minimal examples. We work our way up to new results about a heap-based calling convention and implementations of sophisticated object-capability patterns of the kind previously studied for high-level languages with object-capabilities, demonstrating that the methodology scales to such reasoning.

OBJECTIVE: Exercise has been accepted and generally recommended for the management of type 1 diabetes mellitus (T1D) and for improving the overall quality of life in affected individuals. This meta-analysis was conducted to determine the overall effects of exercise (acute bouts of exercise and chronic exercise [or training]) on acute and chronic glycaemic control in patients with T1D, the effects of different types of exercise on glycaemic control and which conditions are required to obtain these positive effects. METHODS: PubMed, ISI Web of Knowledge and SPORTDiscus™ were consulted to identify studies on T1D and exercise. Cohen's d statistics were used for calculating mean effect sizes (ES) as follows: small d = 0.3, medium d = 0.5 and large d = 0.8. Ninety-five percent confidence intervals (95% CIs) were used to establish the significance of our findings. RESULTS: From a total of 937 studies, 33 that met the inclusion criteria were selected. Nine studies were used to calculate the ES of a single bout of aerobic exercise; 13 studies to calculate the ES of aerobic training; 2 studies to calculate the ES of strength training; 4 studies to calculate the ES of combined (aerobic and strength) training and 6 studies to calculate the ES of high-intensity exercise (HIE) and training. ES for exercise on acute glycaemic control were large, while they were small for chronic glycaemic control. Aerobic exercise, resistance exercise, mixed exercise (aerobic combined with resistance training) and HIE acutely decreased blood glucose levels. To prevent late-onset hypoglycaemic episodes, the use of single bouts of sprints into an aerobic exercise can be recommended. This meta-analysis also showed that a regular exercise training programme has a significant effect on acute and chronic glycaemic control, although not all exercise forms showed significant results. Specifically, aerobic training is a favourable tool for decreasing chronic glycaemic control, while resistance training, mixed and HIE did not significantly improve chronic glycaemic control. Although, this meta-analysis showed there was a tendency for improvement in glycaemic control due to resistance training or resistance training combined with endurance training, there were not enough studies and/or subjects to confirm this statistically. CONCLUSIONS: Based on this meta-analysis, we can conclude that the addition of brief bouts of high-intensity, sprint-type exercise to aerobic exercise can minimize the risk of sustaining a hypoglycaemic episode. We can also conclude that only regular aerobic training will improve the glycated haemoglobin level of a patient with T1D.

International audience; Hippocampal brain-derived neurotrophic factor (BDNF) protein is increased with exercise in rats. Monoamines seem to play a role in the regulation of BDNF, and monoamine neurotransmission is known to increase with exercise. The purpose of this study was to examine the influence of acute exercise on monoaminergic neurotransmission and BDNF protein concentrations. Hippocampal microdialysis was performed in rats that were subjected to 60 min of treadmill running at 20 m/min or rest. Two hours postexercise, the rats were killed, and the hippocampus was dissected. In experiments without microdialysis, hippocampus and serum samples were collected immediately after exercise. Exercise induced a twofold increase in hippocampal dopamine release. Noradrenaline and serotonin release were not affected. Hippocampal BDNF levels were not influenced, whether they were measured immediately or 2 h after the exercise protocol. Serum BDNF levels did not change either, but serum BDNF was negatively correlated to peripheral corticosterone concentrations, indicating a possible inhibitory reaction to the stress of running. Sixty minutes of exercise enhances dopamine release in the hippocampus of the rat in vivo. However, this increase is not associated with changes in BDNF protein levels immediately nor 2 h after the acute exercise bout. An increased corticosterone level might be the contributing factor for the absence of changes in BDNF.

International audience; It is assumed that genetic diseases affecting the metabolism of cysteine and the kidney function lead to two different kinds of pathologies, namely cystinuria and cystinosis whereby generate L-cystine crystals. Recently, the presence of L-cysteine crystal has been underlined in the case of cystinosis. Interestingly, it can be strikingly seen that cystine ([-S-CH2-CH-(NH2)-COOH]2) consists of two cysteine (C3H7NO2S) molecules connected by a disulfide (S-S) bond. Therefore, the study of cystine and cysteine is important for providing a better understanding of cystinuria and cystinosis. In this paper, we elucidate the discrepancy between L-cystine and L-cysteine by investigating the theoretical and experimental infrared spectra (IR), X-ray diffraction (XRD) as well as Raman spectra aiming to obtain a better characterization of abnormal deposits related to these two genetic pathologies.

International audience; This research sought to test the hypothesis that regulatory fit enhances people’s feelings of autonomy. Regulatory fit can be created by prompting people to execute a task using means of task execution that fit (vs. do not fit) their preferred means of goal-pursuit. Assigning people to do a task using a particular means implies they do not exercise choice in applying their preferred means of goal-pursuit. Nevertheless, we reasoned that fitting task means would lead to higher feelings of autonomy while working on a task because, under conditions of regulatory fit, people are using the means that they would have chosen if they had been given choice. We conducted 10 experiments (total N = 3,124) to test the effect of regulatory fit versus regulatory non-fit on experienced autonomy and a meta-analysis of the effects supported our hypothesis for both promotion focus-based fit and prevention focus-based fit.

Streamflow is often the only variable used to evaluate hydrological models. In a previous international comparison study, eight research groups followed an identical protocol to calibrate 12 hydrological models using observed streamflow of catchments within the Meuse basin. In the current study, we quantify the differences in five states and fluxes of these 12 process-based models with similar streamflow performance, in a systematic and comprehensive way. Next, we assess model behavior plausibility by ranking the models for a set of criteria using streamflow and remote-sensing data of evaporation, snow cover, soil moisture and total storage anomalies. We found substantial dissimilarities between models for annual interception and seasonal evaporation rates, the annual number of days with water stored as snow, the mean annual maximum snow storage and the size of the root-zone storage capacity. These differences in internal process representation imply that these models cannot all simultaneously be close to reality. Modeled annual evaporation rates are consistent with Global Land Evaporation Amsterdam Model (GLEAM) estimates. However, there is a large uncertainty in modeled and remote-sensing annual interception. Substantial differences are also found between Moderate Resolution Imaging Spectroradiometer (MODIS) and modeled number of days with snow storage. Models with relatively small root-zone storage capacities and without root water uptake reduction under dry conditions tend to have an empty root-zone storage for several days each summer, while this is not suggested by remote-sensing data of evaporation, soil moisture and vegetation indices. On the other hand, models with relatively large root-zone storage capacities tend to overestimate very dry total storage anomalies of the Gravity Recovery and Climate Experiment (GRACE). None of the models is systematically consistent with the information available from all different (remote-sensing) data sources. Yet we did not reject models given the uncertainties in these data sources and their changing relevance for the system under investigation.

International audience

An integrative approach is crucial in discrimination of species, especially for taxa that are difficult to identify based on morphological characters. In this study, we combine genetics and morphology to assess the diversity of Pterasteridae, a sea star family diversified in deep-sea and polar environments. Because of their derived anatomy and the frequent loss of characters during preservation, Pterasteridae are a suitable case for an integrative study. The molecular identification of 191 specimens (mostly from the Southern Ocean) suggests 26–33 species in three genera (Diplopteraster, Hymenaster and Pteraster), which match the morphological identification in 54–62% of cases. The mismatches are either different molecular units that are morphologically indistinguishable (e.g. Pteraster stellifer units 2 and 4) or, conversely, nominal species that are genetically identical (e.g. Hymenaster coccinatus/densus/praecoquis). Several species are shared between the Northern and Southern Hemispheres (e.g. Pteraster jordani/affinis). In conclusion, the taxonomic status of some groups is confirmed, but for others we find the need to re-evaluate the taxonomy at both genus and species levels. This work significantly increases the DNA barcode library of the Southern Ocean species and merges taxonomic information into an identification key that could become a baseline for future studies (pterasteridae-so.identificationkey.org)., info:eu-repo/semantics/published

Assembly-level protection mechanisms (virtual mem-ory, trusted execution environments, virtualization) make it possible to guarantee security properties of a full system in the presence of arbitrary attacker provided code. However, they typically only support a single trust boundary: code is either trusted or untrusted, and protection cannot be nested. Capability machines provide protection mechanisms that are more fine-grained and that do support arbitrary nesting of protection. We show in this paper how this enables the formal verification of full-system security properties under multiple attacker models: differ-ent security objectives of the full system can be verified under a different choice of trust boundary (i.e. under a different attacker model). The verification approach we propose is modular, and is robust: code outside the trust boundary for a given security objective can be arbitrary, unverified attacker-provided code. It is based on the use of universal contracts for untrusted adversarial code: sound, conservative contracts which can be combined with manual verification of trusted components in a compositional program logic. Compositionality of the program logic also allows us to reuse common parts in the analyses for different attacker models. We instantiate the approach concretely by extending an existing capability machine model with support for memory-mapped 1/0 and we obtain full system, machine-verified security properties about external effect traces while limiting the manual verification effort to a small trusted computing base relevant for the specific property under study. ispartof: pages:80-95 ispartof: 2022 IEEE 35th Computer Security Foundations Symposium (CSF) pages:80-95 ispartof: IEEE Computer Security Foundations Symposium (CSF) location:Haifa, Israel date:7 Aug - 10 Aug 2022 status: published

International audience; INTRODUCTION: The evolution of cavernous sinus meningiomas (CSMs) might be unpredictable and the efficacy of their treatments is challenging due to their indolent evolution, variations and fluctuations of symptoms, heterogeneity of classifications and lack of randomized controlled trials. Here, a dedicated task force provides a consensus statement on the overall management of CSMs. RESEARCH QUESTION: To determine the best overall management of CSMs, depending on their clinical presentation, size, and evolution as well as patient characteristics. MATERIAL AND METHODS: Using the PRISMA 2020 guidelines, we included literature from January 2000 to December 2020. A total of 400 abstracts and 77 titles were kept for full-paper screening. RESULTS: The task force formulated 8 recommendations (Level C evidence). CSMs should be managed by a highly specialized multidisciplinary team. The initial evaluation of patients includes clinical, ophthalmological, endocrinological and radiological assessment. Treatment of CSM should involve experienced skull-base neurosurgeons or neuro-radiosurgeons, radiation oncologists, radiologists, ophthalmologists, and endocrinologists. DISCUSSION AND CONCLUSION: Radiosurgery is preferred as first-line treatment in small, enclosed, pauci-symptomatic lesions/in elderly patients, while large CSMs not amenable to resection or WHO grade II-III are candidates for radiotherapy. Microsurgery is an option in aggressive/rapidly progressing lesions in young patients presenting with oculomotor/visual/endocrinological impairment. Whenever surgery is offered, open cranial approaches are the current standard. There is limited experience reported about endoscopic endonasal approach for CSMs and the main indication is decompression of the cavernous sinus to improve symptoms. Whenever surgery is indicated, the current trend is to offer decompression followed by radiosurgery.

L’article apporte un éclairage inédit sur le projet d’une confédération européenne de Krause publié en juin et juillet 1814. Utopiste et précurseur, ce projet n’a jamais été traduit de l’allemand. Il appartient néanmoins à l’histoire des projets européens dans le contexte du congrès de Vienne et du premier moment du concert européen des puissances. Grâce aux krausistes Ahrens et Leonhardi et à la revue Die Friedens-wärte, le projet n’est pas tombé dans l’oubli et a connu une certaine postérité.

Background: Coronavirus disease 2019 (COVID-19) emerged as a worldwide health crisis, overwhelming healthcare systems. Elevated cardiac troponin T (cTn T) at admission was associated with increased in-hospital mortality. However, data addressing the role of cTn T in major adverse cardiovascular events (MACE) in COVID-19 are scarce. Therefore, we assessed the role of baseline cTn T and cTn T kinetics for MACE and in-hospital mortality prediction in COVID-19. Methods: Three hundred and ten patients were included prospectively . One hundred and eight patients were excluded due to incomplete records. Patients were divided into three groups according to cTn T kinetics: ascending, descending, and constant. The cTn T slope was defined as the ratio of the cTn T change over time. The primary and secondary endpoints were MACE and in-hospital mortality. Results: Two hundred and two patients were included in the analysis (mean age 64.4 ± 16.7 years, 119 [58.9%] males). Mean duration of hospitalization was 14.0 ± 12.3 days. Sixty (29.7%) patients had MACE, and 40 (19.8%) patients died. Baseline cTn T predicted both endpoints ( p = 0.047, hazard ratio [HR] 1.805, 95% confidence interval [CI] 1.009 – 3.231 ; p = 0.009, HR 2.322, 95% CI 1.234 – 4.369) . Increased cTn T slope predicted mortality (p = 0.041, HR 1.006, 95% CI 1.000–1.011). Constant cTn T was associated with lower MACE and mortality (p = 0.000, HR 3.080, 95% CI 1.914–4.954, p = 0.000, HR 2.851, 95% CI 1.828–4.447). Conclusions: The present study emphasizes the additional role of cTn T testing in COVID-19 patients for risk stratification and improved diagnostic pathway and management.

Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or -NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharmacophore Dmt-DALDA (H-Dmt-d-Arg-Phe-Lys-NH2) and the dual μ/δ opioid agonist H-Dmt-d-Arg-Aba-βAla-NH2 (KGOP01). Opioid binding assays unequivocally demonstrated that only hybrids SBL-OPNK-5, SBL-OPNK-7 and SBL-OPNK-9, bearing the KGOP01 scaffold, conserved nanomolar range μ-opioid receptor (MOR) affinity, and slightly reduced affinity for the δ-opioid receptor (DOR). Moreover, NK binding experiments proved that compounds SBL-OPNK-5, SBL-OPNK-7, and SBL-OPNK-9 exhibited (sub)nanomolar binding affinity for NK2 and NK3, opening promising opportunities for the design of next-generation opioid hybrids.

International audience

International audience

International audience; Proteins containing one or more RNA Recognition Motif (RRM) domains perform important regulation functions through binding to specific RNA sequences. Our project is to help design new RRM proteins by providing data-driven rules and knowledge, based on the 3D structures of RRM domains. Protein domain classifications were screened to identify the most comprehensive set of RRM families for which one or more 3D structures are available. We created a master alignment for all available RRM 3D structures using Pfam (PF00076) seed alignment and the Kpax tool. Amino-acid properties and structural descriptors like torsion angles or accessibility were linked to the nucleotide-binding capacity at each position, and compared in RNA bound versus unbound structures. The extracted patterns will help to predict RNA binding propensity at the domain and residue level, and to model the 3D structure of the complex. Such patterns will be tested in vitro/vivo by our collaborators.

The spectroscopic study of pathological calcifications (including kidney stones) is extremely rich and helps to improve the understanding of the physical and chemical processes associated with their formation. While FTIR imaging and optical/electron microscopies are routine techniques in hospitals, there has been a dearth of solid state NMR studies introduced into this area of medical research, probably due to the scarcity of this analytical technique in hospital facilities. This work introduces effective multinuclear and multi-dimensional solid state NMR methodologies to study the complex chemical and structural properties characterising kidney stone composition. As a basis for comparison three hydrates (n = 1, 2 and 3) of calcium oxalate are examined along with nine representative kidney stones. The multinuclear MAS NMR approach adopted investigates the 1H, 13C, 31P and 43Ca nuclei, with the 1H and 13C MAS NMR data able to be readily deconvoluted into the constituent elements associated with the different oxalates and organics present. For the first time, the full interpretation of highly resolved 1H NMR spectra is presented for the three hydrates, based on structure and local dynamics. The corresponding 31P MAS NMR data indicates the presence of low-level inorganic phosphate species, however the complexity of these data make the precise identification of the phases difficult to assign. This work provides physicians, urologists and nephrologists with additional avenues of spectroscopic investigation to interrogate this complex medical dilemma that requires real multi technique approaches to generate effective outcomes.

International audience; Differences in elution strength between the sample solvent and the mobile phase usually give rise to undesirable effects on the chromatographic separation, which may range from slight broadening to severe peak deformation or even splitting. In the most extreme case, the retention factor of the analyte at the head of the column is so small at the time of injection that part of the analyte goes through the column with very little interaction with the stationary phase and hence elutes very close to the column dead time. This phenomenon is known as breakthrough. Usually, during breakthrough, the retained peak displays a wide array of deformations and it is not rare that multiple retained peaks appear for a given injected analyte. However, under certain conditions, it has been demonstrated that these deleterious effects could fully disappear, leaving only one breakthrough peak and one symmetrical peak on the chromatogram. This so-called “total breakthrough” phenomenon was recently highlighted in the specific context of the 2D-LC separation of peptides but has yet to be explained. In the present paper, we describe the results of a comprehensive study aiming to better understand and define the conditions of emergence of both breakthrough and total breakthrough phenomena in liquid chromatography. The effects of a broad range of parameters, including the nature of the solute, the retention mechanism, the injection and elution conditions, the column temperature, and the injected sample concentration on the occurrence of both phenomena were investigated. While breakthrough was found to occur for all studied compounds, it appears that the presence of positive charges on the molecule is a prerequisite for observing a total breakthrough phenomenon. Among all the parameters investigated in this work, only the injection conditions and the analyte retention were found to be impactful on the onset of both phenomena. This finding allowed us to suggest one necessary and sufficient condition, relying on the injection of critical volumes to observe each respective phenomenon. These critical volumes only depend on the column dead volume and the retention factor of the analyte in the injection solvent.

Background: Genome-wide data are invaluable to characterize differentiation and adaptation of natural populations. Reduced representation sequencing (RRS) subsamples a genome repeatedly across many individuals. However, RRS requires careful optimization and fine-tuning to deliver high marker density while being cost-efficient. The number of genomic fragments created through restriction enzyme digestion and the sequencing library setup must match to achieve sufficient sequencing coverage per locus. Here, we present a workflow based on published information and computational and experimental procedures to investigate and streamline the applicability of RRS. Results: In an iterative process genome size estimates, restriction enzymes and size selection windows were tested and scaled in six classes of Antarctic animals (Ostracoda, Malacostraca, Bivalvia, Asteroidea, Actinopterygii, Aves). Achieving high marker density would be expensive in amphipods, the malacostracan target taxon, due to the large genome size. We propose alternative approaches such as mitogenome or target capture sequencing for this group. Pilot libraries were sequenced for all other target taxa. Ostracods, bivalves, sea stars, and fish showed overall good coverage and marker numbers for downstream population genomic analyses. In contrast, the bird test library produced low coverage and few polymorphic loci, likely due to degraded DNA. Conclusions: Prior testing and optimization are important to identify which groups are amenable for RRS and where alternative methods may currently offer better cost-benefit ratios. The steps outlined here are easy to follow for other non-model taxa with little genomic resources, thus stimulating efficient resource use for the many pressing research questions in molecular ecology., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Chemicals of Emerging Concern (CECs) include a very wide group of chemicals that are suspected to be responsible for adverse effects on health, but for which very limited information is available. Chromato-graphic techniques coupled with high-resolution mass spectrometry (HRMS) can be used for non-targeted screening and detection of CECs, by using comprehensive annotation databases. Establishing a database focused on the annotation of CECs in human samples will provide new insight into the distribution and extent of exposures to a wide range of CECs in humans. Objectives: This study describes an approach for the aggregation and curation of an annotation database (CECscreen) for the identification of CECs in human biological samples. Methods: The approach consists of three main parts. First, CECs compound lists from various sources were aggregated and duplications and inorganic compounds were removed. Subsequently, the list was curated by standardization of structures to create & ldquo;MS-ready & rdquo; and & ldquo;QSAR-ready & rdquo; SMILES, as well as calculation of exact masses (monoisotopic and adducts) and molecular formulas. The second step included the simulation of Phase I metabolites. The third and final step included the calculation of QSAR predictions related to physicochemical properties, environmental fate, toxicity and Absorption, Distribution, Metabolism, Excretion (ADME) processes and the retrieval of information from the US EPA CompTox Chemicals Dashboard. Results: All CECscreen database and property files are publicly available (DOI: https://doi.org/10.5281/zenodo. 3956586). In total, 145,284 entries were aggregated from various CECs data sources. After elimination of du-plicates and curation, the pipeline produced 70,397 unique & ldquo;MS-ready & rdquo; structures and 66,071 unique QSAR-ready structures, corresponding with 69,526 CAS numbers. Simulation of Phase I metabolites resulted in 306,279 unique metabolites. QSAR predictions could be performed for 64,684 of the QSAR-ready structures, whereas information was retrieved from the CompTox Chemicals Dashboard for 59,739 CAS numbers out of 69,526 inquiries. CECscreen is incorporated in the in silico fragmentation approach MetFrag. Discussion: The CECscreen database can be used to prioritize annotation of CECs measured in non-targeted HRMS, facilitating the large-scale detection of CECs in human samples for exposome research. Large-scale detection of CECs can be further improved by integrating the present database with resources that contain CECs (metabolites) and meta-data measurements, further expansion towards in silico and experimental (e.g., MassBank) generation of MS/MS spectra, and development of bioinformatics approaches capable of using cor-relation patterns in the measured chemical features.

Over the last few years, immunotherapy for HIV in general and therapeutic vaccination in particular, has received a tremendous boost, both in preclinical research and in clinical applications. This interest is based on the evidence that the immune system plays a crucial role in controlling HIV infection, as shown for long-term non-progressors and elite controllers, and that immune responses can be manipulated towards targeting conserved epitopes. So far, the most successful approach has been vaccination with autologous dendritic cells (DCs) loaded ex vivo with antigens and activation signals. Although this approach offers much promise, it also comes with significant drawbacks such as the requirement of a specialized infrastructure and expertise, as well as major challenges for logistics and storage, making it extremely time consuming and costly. Therefore, methods are being developed to avoid the use of ex vivo generated, autologous DCs. One of these methods is based on mRNA for therapeutic vaccination. mRNA has proven to be a very promising vaccine platform, as the coding information for any desired protein, including antigens and activation signals, can be generated in a very short period of time, showing promise both as an off-the-shelf therapy and as a personalized approach. However, an important drawback of this approach is the short half-life of native mRNA, due to the presence of ambient RNases. In addition, proper immunization requires that the antigens are expressed, processed and presented at the right immunological site (e.g. the lymphoid tissues). An ambivalent aspect of mRNA as a vaccine is its capacity to induce type I interferons, which can have beneficial adjuvant effects, but also deleterious effects on mRNA stability and translation. Thus, proper formulation of the mRNA is crucially important. Many approaches for RNA formulation have already been tested, with mixed success. In this review we discuss the state-of-the-art and future trends for mRNA-nanoparticle formulations for HIV vaccination, both in the prophylactic and in the therapeutic setting.

Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

The biogeochemical behavior of Cd, Co, Cr, Cu, Ni and Pb along the historically polluted Scheldt estuary (Belgium - The Netherlands) was investigated in this study. As never studied before in this area, labile trace metals were measured using the passive sampling technique of Diffusive Gradients in Thin-films (DGT), while total dissolved and particulate trace metal concentrations were assessed using classic active sampling techniques. This dual approach allowed us to highlight the variations of trace metal speciation and distribution in the estuarine surface waters, considering environmental and physicochemical gradients along the transect. The large data set obtained was then compared with literature data of historical measurements along the Scheldt (from 1980 until now), but also from other estuaries. As emphasized by our results, trace metal mobility and partitioning along the Scheldt estuary was mainly driven by biogeochemical reactions which were strongly influenced by gradients of specific estuarine physico-chemical parameters, such as salinity, turbidity, temperature and so on. . Hence, all species of trace metals displayed a non-conservative behavior. More precisely, dissolved labile fractions of trace metals showed higher levels in the middle estuary, where many solubilization and remobilization processes occurred due to turbulent mixing mechanisms and an increasing salinity. Our study confirmed the decreasing trend historically observed for particulate metals along the Scheldt, as well as the rising concentrations recorded for dissolved trace metals which might also lead to an increase of their labile fraction measured by the DGT. Finally, these preliminary results suggested that a more regular monitoring of labile metal along the Scheldt estuary is essential to have an in-depth understanding of trace metal speciation and to review bioavailability of trace metals within estuarine ecosystems.

Encrusted uropathy is a rare subacute to chronic inflammatory disorder caused by infection with urease-producing bacteria, mainlyCorynebacterium urealyticum. The disorder is characterized by urothelial deposition of struvite and carbonated apatite, resulting in encrustations and ulceronecrotic inflammation of the urothelium and surrounding tissues. Most commonly, encrusted uropathy is encountered in patients with predisposing conditions. The disease remains underdiagnosed. High urinary pH and negative conventional urine cultures should raise suspicion of the diagnosis. Prognosis is dependent on timely diagnosis and treatment installment, which consists of urological removal of encrustations in combination with urinary acidification and long-term antibiotic therapy.

20 pages, 11 figures, 3 tables; We present a pioneering estimate of the global yearly greenhouse gas emissions of a large-scale Astrophysics experiment over several decades: the Giant Array for Neutrino Detection (GRAND). The project aims at detecting ultra-high energy neutrinos with a 200,000 radio antenna array over 200,000 km$^2$ as of the 2030s. With a fully transparent methodology based on open source data, we calculate the emissions related to three unavoidable sources: travel, digital technologies and hardware equipment. We find that these emission sources have a different impact depending on the stages of the experiment. Digital technologies and travel prevail for the small-scale prototyping phase (GRANDProto300), whereas hardware equipment (material production and transportation) and data transfer/storage largely outweigh the other emission sources in the large-scale phase (GRAND200k). In the mid-scale phase (GRAND10k), the three sources contribute equally. This study highlights the considerable carbon footprint of a large-scale astrophysics experiment, but also shows that there is room for improvement. We discuss various lines of actions that could be implemented. The GRAND project being still in its prototyping stage, our results provide guidance to the future collaborative practices and instrumental design in order to reduce its carbon footprint.

Background: Coronary artery disease distribution along the vessel is a main determinant of FFR improvement after PCI. Identifying focal from diffuse disease from visual inspections of coronary angiogram (CA) and FFR pullback (FFR-PB) are operator-dependent. Computer science may standardize interpretations of such curves.Methods: A virtual stenting algorithm (VSA) was developed to perform an automated FFR-PB curve analysis. A survey analysis of the evaluations of 39 vessels with intermediate disease on CA and a distal FFR Results: Inter-rater reliability in vessel disease assessment by CA, CA/FFR-PB, and CA/VSA were respectively, 0.32 (95% CI: 0.17–0.47), 0.38 (95% CI: 0.23–0.53), and 0.4 (95% CI: 0.25–0.55). The raters' overall agreement in vessel disease distribution and PCI eligibility was higher with the VSA than with the operator (respectively, 67 vs. 42%, and 80 vs. 70%, both p < 0.05). Compared to CA/FFR-PB, CA/VSA induced more reclassification toward a focal disease (92 vs. 56.2%, p < 0.01) with a trend toward more reclassification as eligible for PCI (70.6 vs. 33%, p = 0.06). Change in PCI strategy did not differ between CA/FFR-PB and CA/VSA (23.6 vs. 28.5%, p = 0.38).Conclusions: VSA is a new program to facilitate and standardize the FFR pullback curves analysis. When expert reviewers integrate VSA data, their assessments are less variable which might help to standardize PCI eligibility and strategy evaluations.Clinical Trial Registration:https://www.clinicaltrials.gov/ct2/show/NCT03824600.

Objective Atrial fibrillation (AF) recurrence occurs in approximately 25% of the patients undergoing cryoballoon ablation (CBA), leading to repeated ablations and complications. Left atrial (LA) dilation has been proposed as a predictor of AF recurrence. However, LA strain is a surrogate marker of LA mechanical dysfunction, which might appear before the enlargement of the LA. The purpose of this study was to evaluate the additional predictive value of LA function assessed using strain echocardiography for AF recurrence after CBA. Methods 172 consecutive patients (62.2 ± 12.2 years, 61% male) were prospectively analyzed. Echocardiography was performed before CBA. Blanking period was defined as the first three months post-ablation. The primary endpoint was AF recurrence after the blanking period. Results 50 (29%) patients had AF recurrence. In the overall study population, peak atrial longitudinal strain (PALS) ≤ 17% had the highest incremental predictive value for AF recurrence (HR = 9.45, 95%CI: 3.17–28.13, p < 0.001). In patients with non-dilated LA, PALS≤17% remained an independent predictor of AF recurrence (HR = 5.39, 95%CI: 1.66–17.52, p = 0.005). Conclusions This study showed that LA function assessed by PALS provided an additional predictive value for AF recurrence after CBA, over LA enlargement. In patients with non—dilated LA, PALS also predicted AF recurrence. These findings emphasize the added value of LA strain, suggesting that it should be implemented in the systematic evaluation of AF patients before CBA.

International audience

A new paleoclimate record from Cyprus gives valuable insights into climatic variations during Marine Isotope Stages (MIS) 6–5 for the East Mediterranean region. Two stalagmites from Pentadactylos cave in the Kyrenia mountain range (800 m altitude) in Cyprus grew from 174.6 ± 0.7 to 112.2 ± 0.5 ka BP with major hiatuses at 163–142 and 132–128 ka. During early MIS6 the stalagmite suggests through a relatively low growth rate (57–5 mm/ka) and variable, but rather negative d18O that climate conditions were highly variable on a millennial scale, with wet and cold climate conditions during Sapropel 6 deposition. At the end of MIS6 (141–132 ka), growth rate varied from 123 to 18 mm/ka and less negative δ 18 O c suggests general dry/cold conditions followed by a growth stop during H11. The onset of MIS5e is marked by the highest growth rate (217 mm/ka). The most negative δ18O values at the onset and during the Eemian wet period in Cyprus are driven mostly by the source effect (Sapropel 5) and enhanced rainfall amounts. Stable conditions during MIS 5e were rather short as shown in the growth and isotopic signal, consistent with other EM records. After 122 ka, growth decreased drastically (8–2 mm/ka) and a slow deterioration of the soil cover is suggested from continuously less negative δ13C values. Fluid inclusion d18O shows a clear shift (4–5‰) between end-MIS 6 and MIS 5e. Clumped isotopes measurements indicate kinetic effects between calcite and water of up to ∼1‰. After correction for kinetic effects using Δ47, a minimum estimate for the MIS 6–5 temperature shift in the EM is ca. 9 °C. Similarly, drastic changes in rainfall amounts are inferred from measured (fluid inclusion) and calculated water d18O.

Neutron stars are likely surrounded by gas, debris, and asteroid belts. Kozai-Lidov perturbations, induced by a distant, but gravitationally bound companion, can trigger the infall of such orbiting bodies onto a central compact object. These effects could lead to the emission of fast radio bursts (FRBs), for example by asteroid-induced magnetic wake fields in the wind of the compact object. A few percent of binary neutron star systems in the Universe, such as neutron star-main sequence star, neutron star-white dwarf, double neutron star, and neutron star-black hole systems, can account for the observed non-repeating FRB rates. More remarkably, we find that wide and close companion orbits lead to non-repeating and repeating sources, respectively, and they allow for one to compute a ratio between repeating and non-repeating sources of a few percent, which is in close agreement with the observations. Three major predictions can be made from our scenario, which can be tested in the coming years: 1) most repeaters should stop repeating after a period between 10 years to a few decades, as their asteroid belts become depleted; 2) some non-repeaters could occasionally repeat, if we hit the short period tail of the FRB period distribution; and 3) series of sub-Jansky level short radio bursts could be observed as electromagnetic counterparts of the mergers of binary neutron star systems., 21 pages, 7 figures, 3 appendices, accepted in A&A (November 26 2020)

International audience; Debugging applications that execute within a framework is not always easy: the call-stack offered to developers is often a mix-up of stack frames that belong to different frameworks, introducing an unnecessary noise that prevents developers from focusing on the debugging task. Moreover, relevant application code is not always available in the call-stack because it may have already returned, or is available in another thread. In such cases, manually gathering all relevant information from these different sources is not only cumbersome but also costly. In this paper we introduce Sarto, a call-stack instrumentation layer that allows developers to tailor the stack to make debugging framework-aware. The goal is to improve the quality and amount information present in the call-stack to reduce debugging time without impacting the execution time. Sarto proposes a set of six stack operations that combined hide irrelevant information, introduce missing information, and relate dispersed debugging sources before this is fed to the debugger. We validate Sarto by applying it to four application cases using inherently different frameworks: unit testing, web server, remote promises and big data processing. We showcase our experiences in using Sarto in the different frameworks, and perform some performance benchmarks to demonstrate that Sarto does not generate noticeable overhead when instrumenting a call-stack. We also show that our solution reduces by half the amount of data stored to debug similar exceptions happening in a parallel setup. CCS Concepts: • Software and its engineering → Application specific development environments; Integrated and visual development environments; Error handling and recovery; Software testing and debugging.

International audience; Fusion of nonopioid pharmacophores, such as neurotensin, with opioid ligands represents an attractive approach for pain treatment. Herein, the μ-/δ-opioid agonist tetrapeptide H-Dmt-D-Arg-Aba-β-Ala-NH 2 (KGOP01) was fused to NT(8-13) analogues. Since the NTS1 receptor has been linked to adverse effects, selective MOR-NTS2 ligands are preferred. Modifications were introduced within the native NT sequence, particularly a β 3-homo amino acid in position 8 and Tyr 11 substitutions. Combination of β 3 hArg and Dmt led to peptide 7, a MOR agonist, showing the highest NTS2 affinity described to date (K i = 3 pM) and good NTS1 affinity (K i = 4 nM), providing a >1300-fold NTS2 selectivity. The (6-OH)Tic-containing analogue 9 also exhibited high NTS2 affinity (K i = 1.7 nM), with low NTS1 affinity (K i = 4.7 μM), resulting in an excellent NTS2 selectivity (>2700). In mice, hybrid 7 produced significant and prolonged antinociception (up to 8 h), as compared to the KGOP01 opioid parent compound.

La présente Note de Politique propose un modèle de rapport du processus d’analyse d’impact relative à la protection des données (AIPD) dans l’Union européenne (UE). Basé sur le cadre et la méthode pour l’analyse d’impact précédemment élaborés (voir respectivement la Note de Politique N° 1/2017 et la Note de Politique N° 1/2019), le modèle proposé est conforme aux exigences des Articles 35–36 du Règlement Général sur la Protection des Données (RGPD) et reflète les meilleures pratiques relatives à l’analyse d’impact. Il présente en outre cinq nouveaux aspects. Premièrement, il vise l’exhaustivité afin de fournir les conseils les plus avisés et robustes possibles pour la prise de décision. Deuxièmement, il vise l’efficacité, dans le sens où il veut produire des effets tout en utilisant le moins de ressources possible. Troisièmement, il vise à examiner et accommoder les points de vue des différentes parties prenantes, même si le point de vue des particuliers sera prédominant. Pour cette raison, il favorise la réflexion sur les droits fondamentaux, notamment en exigeant une justification pour chaque choix à réaliser, ce qui va au-delà d’une simple opération consistant à « cocher une case ». Quatrièmement, il vise à adopter l’approche de « legal design » afin de guider les évaluateurs d’une manière pratique, aisée et intuitive à travers les 11 étapes du processus d’analyse en fournissant les explications nécessaires à chaque étape, tout en offrant une structure composée de champs à compléter et de tableaux extensibles et modifiables. Cinquièmement, il accepte de ne pas être définitif du fait qu’il devra être révisé au fur et à mesure de l’expérience acquise lors de son utilisation. Le modèle est principalement destiné aux évaluateurs auxquels les responsables du traitement de données ont confié la réalisation du processus d’analyse, mais il peut également aider les autorités de protection des données (APD) au sein de l’UE à développer (adapter) des modèles pour les AIPD se rapportant au champ de leurs propres compétences.

International audience; Objective Countertransference in forensic inpatient settings has received little empirical attention despite frequent emotional reactions in staff members, such as anger, disgust, or fear. In this exploratory study, we investigated countertransference in two forensic medium-secure units for patients with psychotic disorders.Method We measured countertransference using the Therapist Response Questionnaire and measured staff personality using the Ten-Item Personality Inventory. Our design allowed all staff members to participate anonymously.Results One hundred thirty-four Therapist Response Questionnaire forms, along with data on patient and staff characteristics, were collected. Staff characteristics such as profession, experience, and personality were associated with different countertransference reactions. Psychologists and psychiatrists tended to report more countertransference feelings than nursing staff. Patient and staff variables (such as patient having committed violent offenses or a diagnosis of personality disorder and staff experience or gender) were associated with more negative countertransference feelings and subscale scores as well as less positive countertransference feelings such as parental, protective, and satisfying countertransference feelings. Some patient and staff variables (such as patient cooperativeness, staff personality trait agreeableness) had the inverse effect on countertransference feelings.Conclusion We discussed several conceptual problems inherent to measuring countertransference (in forensic inpatient settings) and the clinical implications of our findings.; Objectif Le contre-transfert en milieu psychiatrique médico-légal a reçu peu d'attention dans la littérature malgré les réactions émotionnelles fréquentes chez les membres du personnel, telles que la colère, le dégoût ou la peur. Dans cette étude exploratoire, nous avons examiné le contre-transfert dans deux unités médico-légales de moyenne sécurité pour des patients souffrant de troubles psychotiques.Méthode Nous avons mesuré le contre-transfert à l'aide du Therapist Response Questionnaire et la personnalité du personnel à l'aide du Ten-Item Personality Inventory. Notre conception a permis à tous les membres du personnel de participer de manière anonyme.Résultats Cent trente-quatre formulaires du Therapist Response Questionnaire, ainsi que des données sur les caractéristiques des patients et du personnel, ont été collectés. Les caractéristiques du personnel telles que la profession, l'expérience et la personnalité ont été associées à différentes réactions de contre-transfert. Les psychologues et les psychiatres ont eu tendance à rapporter plus de sentiments de contre-transfert que le personnel infirmier. Les variables relatives au patient et au personnel (telles que le fait que le patient ait commis des délits violents ou un diagnostic de trouble de la personnalité et l'expérience ou le sexe du personnel) étaient associées à des sentiments de contre-transfert et à des scores de sous-échelle plus négatifs, ainsi qu'à des sentiments de contre-transfert moins positifs tels que les sentiments de contre-transfert parentaux, protecteurs et satisfaisants. Certaines variables du patient et du personnel (telles que la coopération du patient, l'agréabilité du personnel) ont eu un effet inverse sur les sentiments de contre-transfert.Conclusion Nous avons discuté de plusieurs problèmes conceptuels inhérents à la mesure du contre-transfert (en milieu médico-légal) et des implications cliniques de nos résultats.

International audience; Background: Infective endocarditis (IE) is a life-threatening disease. Despite advancements in diagnostic methods, the initial clinical presentation of IE remains a valuable asset. Therefore, the impact of clinical presentation on outcomes and its association with microorganisms and IE localization were assessed herein. Methods: This retrospective study included 183 patients (age 68.9 ± 14.2 years old, 68.9% men) with definite IE at two tertiary care hospitals in Belgium. Demographic data, medical history, clinical presentation, blood cultures, imaging data and outcomes were recorded. Results: In-hospital mortality rate was 22.4%. Sixty (32.8%) of the patients developed embolism, 42 (23%) shock, and 103 (56.3%) underwent surgery during hospitalization. Shock at admission predicted embolism during hospitalization (odds ratio [OR] 2.631, 95% confidence interval [CI] 1.119-6.184, p = 0.027). A new cardiac murmur at admission predicted cardiac surgery (OR 1.949, 95% CI 1.007-3.774, p = 0.048). Methicillin resistant Staphylococcus aureus predicted in-hospital mortality and shock (p = 0.005, OR 6.945, 95% CI 1.774-27.192 and p = 0.015, OR 4.691, 95% CI 1.348-16.322, respectively). Mitral valve and aortic valve IE respectively predicted in-hospital death (p = 0.039, OR 2.258, 95% CI 1.043-4.888) and embolism (p = 0.017, OR 2.328, 95% CI 1.163-4.659). Conclusions: In this retrospective study, shock at admission independently predicted embolism during hospitalization in IE patients. Moreover, a new cardiac murmur at admission predicted the need for cardiac surgery. This emphasizes the importance of a comprehensive initial clinical evaluation in combination with imaging and microbiological data, in order to identify high-risk IE patients early.

International audience

International audience

Laminar flame speeds of ammonia with oxygen-enriched air (oxygen content varying from 21 to 30 vol.%) and ammonia-hydrogen-air mixtures (fuel hydrogen content varying from 0 to 30 vol.%) at elevated pressure (1-10 bar) and temperature (298-473 K) were determined experimentally using a constant volume combustion chamber. Moreover, ammonia laminar flame speeds with helium as an inert were measured for the first time. Using these experimental data along with published ones, we have developed a newly compiled kinetic model for the prediction of the oxidation of ammonia and ammonia-hydrogen blends in freely propagating and burner stabilized premixed flames, as well as in shock tubes, rapid compression machines and a jet-stirred reactor. The reaction mechanism also considers the formation of nitrogen oxides, as well as the reduction of nitrogen oxides depending on the conditions of the surrounding gas phase. The experimental results from the present work and the literature are interpreted with the help of the kinetic model derived here. The experiments show that increasing the initial temperature, fuel hydrogen content, or oxidizer oxygen content causes the laminar flame speed to increase, while it decreases when increasing the initial pressure. The proposed kinetic model predicts the same trends than experiments and a good agreement is found with measurements for a wide range of conditions. The model suggests that under rich conditions the N 2 H 2 formation path is favored compared to stoichiometric condition. The most important reactions under rich conditions are: NH 2 + NH = N 2 H 2 + H, NH 2 + NH 2 = N 2 H 2 + H 2 , N 2 H 2 + H = NNH + H 2 and N 2 H 2 + M = NNH + H + M. These reactions were also found to be among the most sensitive reactions for predicting the laminar flame speed for all the cases investigated.

In recent years, the adverse effects of drought have been experienced and perceived more severely and frequently all over Europe. These impacts are a result of the drought hazard and the socio-economic and ecological vulnerability. Due to the heterogeneity of Europe’s hydro-climatology and its cultural, political, social and economic diversity , the socio-economic and ecological impacts vary not only with respect to the extent, duration and severity of the drought, but also with the characteristics of affected societies, economic sectors and ecosystems. The lack of understanding the spatio-temporal differences in the drivers of drought risk hinders the successful mitigation of future impacts, and the design of suitable reactive and proactive drought action plans. Therefore, this study describes the European drought events of 2018 and 2019 beyond the hazard. The hypothesis to be proven is that similar hazard conditions result in different impacts due to national and sub-national differences in drought vulnerability, perception and drought-risk management. Based on research in 35 European countries, comparable national datasets on drought management and perception are established. For each of these countries, a uniform questionnaire was distributed to water management-related stakeholders at different administrative levels. A major focus of the questions was the perception and impacts of the recent droughts and current management strategies on a national and sub-national scale. The results of the questionnaires are also compared to country-scale profiles of past drought events for different drought types, i.e. meteorological, soil moisture, hydrological and vegetation drought, which were established based on information derived from the European Drought Observatory indicator system.The results highlight a large diversity in the national perception of drought as a natural hazard and its impacts; but also a different spatial extent of 2018/2019 drought events At the same time, existing drought management strategies are shown to increase national and sub-national resilience. The study, therefore, calls for international exchange and mutual learning to improve national and international drought governance and management.